Liposomes containing oligopeptide fragments of myelin basic protein, a pharmaceutical composition and a method for treatment of multiple sclerosis

a technology of myelin basic protein and liposome, which is applied in the direction of peptide/protein ingredients, peptide sources, immunodeficiency disorders, etc., can solve the problems of inflammatory demyelinating lesions in the brain and spinal cord, no existing therapies are capable of curing or preventing ms progression, and the formation of demyelination scarring and other problems, to achieve the effect of reducing paralysis, improving the intake of thes

Inactive Publication Date: 2013-03-07
LIPOXEN TECHNOLOGIES LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The present invention is based, in part, on the discovery that certain MBP peptides are major B cell epitopes in patients suffering from multiple sclerosis. It was found that administration of liposomal formulations of these peptides, but not the free peptides, to rodent models of MS resulted in a statistically significant red...

Problems solved by technology

Multiple sclerosis (MS) is neurodegenerative disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring.
Approximately one million people worldwide suffer from this autoimmune disease, which has an enigmatic etiology and poorly understood pathogenesis.
Infiltration of th...

Method used

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  • Liposomes containing oligopeptide fragments of myelin basic protein, a pharmaceutical composition and a method for treatment of multiple sclerosis
  • Liposomes containing oligopeptide fragments of myelin basic protein, a pharmaceutical composition and a method for treatment of multiple sclerosis
  • Liposomes containing oligopeptide fragments of myelin basic protein, a pharmaceutical composition and a method for treatment of multiple sclerosis

Examples

Experimental program
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Effect test

example 1

Preparation of Liposomes Containing MBP Peptides by Sonication

[0226]45 g of a phospholipid mixture containing 1 part by weight of mannosylated DOG lipid (ManDOG) and 99 parts by weight of 2,3-dipalmitoyl-sn-glycero-1-phosphatydyl choline was dissolved in 450 mL of chloroform and placed in a 1 L vacuum evaporator flask. The chloroform was evaporated under vacuum to form a lipid film on the flask walls. After evaporation, the flask was filled with nitrogen gas, and 800 mL of water for injections (WFI) was slowly introduced therein. The flask was placed in the ultrasonic bath for 30 minutes to disrupt pre-formed liposomes. Liposomes re-formed after sonication, resulting in an aqueous emulsion of liposomes.

[0227]0.75 g of an MBP peptide mixture containing GGDRGAPKRGSGKDSHH (SEQ ID NO:1; MBP1), GFGYGGRASDYKSAHK (SEQ ID NO:2; MBP2), and QGTLSKIFKLGGRDSRSGSPMARR (SEQ ID NO:3; MBP3) and excess lactose (lactose to lipid ratio of 3:1) in equal amounts was then dissolved in 40 mL of water for ...

example 2

Preparation of Liposomes Containing MBP Peptides Via Disintegration

[0229]45 g of a phospholipid mixture containing 1 part by weight of mannosylated DOG lipid (ManDOG) and 99 parts by weight of 2,3-dipalmitoyl-sn-glycero-1-phosphatydyl choline was dissolved in 450 mL of chloroform and placed in a 1 L vacuum evaporator flask. The chloroform was evaporated under vacuum to form a lipid film on the flask walls. After evaporation, the flask was filled with nitrogen gas, and 800 mL of water for injections was slowly introduced therein. The resulting mixture is transferred to a flowing disintegrator receiver and the stroke volume pressure of the disintegrator is set at 150 MPa. 100 ml. of the mixture is added to the flowing disintegrator per load, and the resulting liposomal emulsion is collected from the disintegrator receiver.

[0230]0.75 g of an MBP peptide mixture containing GGDRGAPKRGSGKDSHH (SEQ ID NO:1; MBP1), GFGYGGRASDYKSAHK (SEQ ID NO:2; MBP2), and QGTLSKIFKLGGRDSRSGSPMARR (SEQ ID N...

example 3

Aqueous Formulation of Liposomes Containing MBP Peptides

[0232]100 mL of buffered phosphate saline solution (FBR) was added to 1000 mg of lyophilized MBP-peptide liposomes, prepared as described in Example 1, under sterile conditions and stirred. Beta-carotene was added then added to the composition at a final concentration of 0.01%, as an antioxidant. The liposome composition was then dispensed into hydrolytic class I glass containers under sterile conditions and a nitrogen atmosphere. The containers were subsequently sealed with rubber plugs and fitted with aluminum caps.

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Abstract

The present invention provides compositions and methods for the treatment of multiple sclerosis. Among others, the invention provides compositions of immunodominant peptides of myelin basic protein encapsulated in mannosylated liposomes. In a specific embodiment, the compositions comprise mylein basic protein (MBP) peptides MBP(46-62), MBP(124-139), and MBP(147-170).

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]The present application claims priority to International Application Serial Number PCT / RU2010 / 000710, filed on Nov. 29, 2010 and Russian Patent Application Serial Number RU 2009145056, filed on Nov. 30, 2009, the disclosures of which are hereby expressly incorporated by reference in their entireties for all purposes.BACKGROUND OF THE INVENTION[0002]Multiple sclerosis (MS) is neurodegenerative disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring. The damage caused to the central nerve system (CNS) results in a wide spectrum of neurological symptoms. Approximately one million people worldwide suffer from this autoimmune disease, which has an enigmatic etiology and poorly understood pathogenesis. B- and T-cells reactive against components of the myelin membrane mediate the demyelination of the brain and spinal cord and appear to be responsible for a large ...

Claims

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Application Information

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IPC IPC(8): C07K17/00A61K38/16C07K19/00A61K9/127A61P25/00A61K38/02C07K17/10B82Y5/00
CPCA61K9/0019A61K38/1709A61K9/127A61P25/00A61P25/28A61P37/00A61K38/10A61K38/16
Inventor GABIVOV, ALEXANDERBELOGUROV, ALEXEYPONOMARENKO, NATALIASMIRNOV, IVANBACON, ANDREWGREGORIADIS, GREGORY
Owner LIPOXEN TECHNOLOGIES LTD
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